Ventral hippocampal kappa opioid receptors mediate the renewal of fear following extinction in the rat

PLoS One. 2013 May 10;8(5):e58701. doi: 10.1371/journal.pone.0058701. Print 2013.

Abstract

The hippocampus is part of a neural network which regulates the renewal of fear following extinction. Both the ventral (VH) and dorsal (DH) hippocampus have been shown to be necessary for renewal, however the critical receptors and neurotransmitters mediating these contributions are poorly understood. One candidate mechanism is the kappa opioid receptor (KOR) system, which has been implicated in fear learning and anxiety. Here we examined the effect of the KOR antagonist norbinaltorphamine hydrochloride (norBNI), infused into either the VH or DH, on the renewal of extinguished fear. We found that an infusion of norBNI into the VH significantly reduced the relapse of fear on test compared to that seen in saline controls (Experiment 1), while similar infusions of norBNI into the DH had no effect on renewal (Experiment 2). These findings show that hippocampal KORs are involved in fear renewal and also identify a dissociation in the contribution of VH and DH KORs to the expression of renewed fear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Extinction, Psychological*
  • Fear / drug effects
  • Fear / physiology*
  • Fear / psychology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Rats
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism*

Substances

  • Narcotic Antagonists
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone

Grants and funding

This work was supported by an Australian Research Council award to Rick Richardson and Gavan P. McNally (DP0880854) (http://www.arc.gov.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.